Despite the important contributions of both epidemiologic and basic science research during the past decade, important gaps exist in our current understanding of both the natural history and pathogenesis of HIV infection. Most recently, the substantial clinical efficiency of protease inhibitors has clearly been shown to extent significantly disease-free survival and death, as a result of dramatic reductions in HIV viral load. However, the exact virologic changes and immunological mechanisms which contribute to long-term survival are still unknown. We therefore propose to continue the Pittsburgh portion of the MACS by further intensive follow-up of a selected, HIV-infected cohort in order to further scientific understanding of the natural history and pathogenesis of HIV infection. The specific objectives and research plan emphasize the cohort-maintenance and biological specimen procurement aspects of the proposed continuation of the Pittsburgh MACS. Additional specific aims will focus on the strengths of the Pittsburgh investigators through collaborations in the areas of HIV viral load dynamics, HIV-specific cellular immune responses, sexual transmission dynamics and the newly identified lipodystrophy associated with HAART treatment modalities. We also propose to provide the MACS-wide coordination of the malignancy/autopsy program in order to investigate the incidence and determinants of cancer in HIV-infected gay/bisexual men. This includes storage of all MACS autopsies, SNOMED coding and distribution of autopsy tissue for research proposals to MACS and non- MACS investigators.